Incidence of Different Characters of Neuropathic Pain in Cancer Patients Coming to Tertiary Care Centre in North India Over A Period of 1 Year - An Observational Study.

Objectives: Pain is classified as nociceptive, neuropathic, or nociplastic. Neuropathic pain presents as variable phenotypes (characters) based on specific aetiology and pathophysiology. This study aimed to find out among cancer patients the incidence of different phenotypes of neuropathic pain and form specific phenotypic clusters based on the underlying neurophysiology and association of sensory profile with various organ systems - A prospective observational study. Materials and methods: The Institutional Ethical Committee clearance (IEC code: 2020-49-MD-EXP-15) https://ctri.nic.in/Clinicaltrials/showallp.php?mid1=44886&EncHid=88651.15716&userName=CTRI/2020/09/027964 approval was obtained. After written and informed consent, patients of age group 18-80 years, registering in the pain and palliative outpatient department or radiotherapy department with complaints of pain and not taking any anti-neuropathic pain medications, were enrolled. They were assessed using Leeds assessment of neuropathic symptoms and signs (LANSS) pain score, and a score of >12 was eligible for assessment of neuropathic pain phenotypes. Results: Out of 210 cancer patients complaining of pain, a neuropathic component with LANSS >12 was found in 73 (34.76%). The most predominant phenotypes, allodynia> tingling> pricking = burning, were found in 72.60%, 56.16%, and 43.84% of patients, respectively. Phenotypes were clustered into Nodes 1 and 2 based on clinically significant separation of phenotypes. Node 1 had neuropathic pain of spontaneous origin found predominantly in gastrointestinal tract (GIT) and genitourinary tract (GUT) cancers. Node 2 had stimulus-evoked negative and positive characters which occurred in head and neck, thoracic, and spinal metastatic cancers. Conclusion: Careful patient assessment reveals the incidence of neuropathic pain in 34.76%; allodynia and tingling astable the most prominent phenotypes. Broadly, sensory characters were clustered into spontaneous and stimulus-evoked sensations with GIT and GUT cancers presenting with Node 1 symptoms.

Modulation of mRNA Expression of IL-6 and mTORC1 and Efficacy and Feasibility of an Integrated Approach Encompassing Cognitive Behavioral Therapy Along with Pregabalin for Management of Neuropathic Pain in Postherpetic Neuralgia: A Pilot Study.

OBJECTIVE: This study was designed to explore the efficacy and feasibility of cognitive behavioral therapy (CBT) along with pregabalin and compare it with pregabalin monotherapy for the management of neuropathic pain in post-herpetic neuralgia (PHN) patients and to explore the modulation of messenger RNA (mRNA) expression of interleukin (IL)-6 and mammalian target of rapamycin-1 (mTORC1) genes in these patients. DESIGN: Randomized controlled pilot study. METHODS: The patients aged >18 years of age with an established diagnosis of PHN with evident allodynia and hyperalgesia who had pain for at least 3 months after healing of rash with pain intensity ≥4/10 on NRS-Pain Scale were enrolled. The trial was registered with the Clinical Trials Registry-India (CTRI/2019/03/018014). A detailed baseline assessment regarding type and duration of pain and disability using pain-relevant self-report questionnaires was done. Two mL venous blood samples were collected for gene expression studies at base line and at end of 12 weeks of treatment. Patients were randomized into one of the two groups. Group PR received pregabalin and Group CP received CBT along with pregabalin. The pain intensity was measured using numeric rating scale (NRS)-Pain scale, neuropathic component of the pain by using Neuropathic Pain Symptom Inventory (NPSI) and Pain Detect Questionnaire (PDQ), sleep interference by NRS-Sleep, pain-related catastrophic thoughts by using Pain Catastrophizing Scale (PCS), depression and quality of life using Beck Depression Inventory-II (BDI-II) and Short Form-12 (SF-12), respectively. The research funding was supported by the intramural grant from the institution. RESULTS: A total of 40 patients with 20 in each group were included. Following integrated approach encompassing CBT and Pregabalin, group CP had significant downregulation of mRNA expression of IL-6; however, no such correlation was observed with mTOR expression. A significant decline in the intensity of pain, NPSI scoring for burning, allodynia, and pain-related catastrophizing were observed; also a significant improvement in depressive symptoms and quality of life were observed with the use of CBT. CONCLUSIONS: A significant downregulation of mRNA expression of IL-6 was observed; however, no significant correlation was observed between NRS pain score and ΔCt values of mRNA expression of both mTORC1 gene and IL-6 gene at baseline and at the end of 12th week. In addition, we note a significant decrease in pain intensity, depressive symptoms, and pain-related catastrophizing while improving QOL was observed with the use of CBT as a clinical adjunct along with pregabalin in PHN patients.

An orally available Cav2.2 calcium channel inhibitor for the treatment of neuropathic pain.

BACKGROUND AND PURPOSE: Neuropathic pain affects up to 10% of the global population and is caused by an injury or a disease affecting the somatosensory, peripheral, or central nervous system. NP is characterized by chronic, severe and opioid-resistant properties. Therefore, its clinical management remains very challenging. The N-type voltage-gated calcium channel, Cav2.2, is a validated target for therapeutic intervention in chronic and neuropathic pain. The conotoxin ziconotide (Prialt®) is an FDA-approved drug that blocks Cav2.2 channel but needs to be administered intrathecally. Thus, although being principally efficient, the required application route is very much in disfavour. EXPERIMENTAL APPROACH AND KEY RESULTS: Here, we describe an orally available drug candidate, RD2, which competes with ziconotide binding to Cav2.2 at nanomolar concentrations and inhibits Cav2.2 almost completely reversible. Other voltage-gated calcium channel subtypes, like Cav1.2 and Cav3.2, were affected by RD2 only at concentrations higher than 10 µM. Data from sciatic inflammatory neuritis rat model demonstrated the in vivo proof of concept, as low-dose RD2 (5 mg·kg-1) administered orally alleviated neuropathic pain compared with vehicle controls. High-dose RD2 (50 mg·kg-1) was necessary to reduce pain sensation in acute thermal response assessed by the tail flick test. CONCLUSIONS AND IMPLICATIONS: Taken together, these results demonstrate that RD2 has antiallodynic properties. RD2 is orally available, which is the most convenient application form for patients and caregivers. The surprising and novel result from standard receptor screens opens the room for further optimization into new promising drug candidates, which address an unmet medical need.

Pulsed Radiofrequency in the Management of Postsurgical Abdominal Wall Chronic Pain: A Report From a Single Oncological Center.

Chronic postsurgical pain (CPSP) is defined as pain that develops or increases in intensity after a surgical procedure or tissue injury and persists beyond the healing process, lasting at least three months after the precipitating event. Often neuropathic in nature, CPSP can be challenging to manage. CPSP is a common complication, with data suggesting an incidence ranging from 5% to 85%, depending on the type of procedure. Meralgia paresthetica (MP) and ilioinguinal/iliohypogastric neuralgias (IH/IL N) are two possible clinical scenarios of CPSP following lower abdominal procedures. Pulsed radiofrequency (PRF) is a minimally invasive technique of peripheral neuromodulation effective in various pain etiologies; however, evidence is scarce regarding its use in MP and IH/IL N. This case series aims to assess the potential role of PRF in the management of CPSP following abdominal wall procedures. This case series was set in a single oncological center between January 2017 and February 2022 and included adult patients (>18 years old) referred to our unit with a high suspicion of postsurgical MP or IH/IL N refractory to conservative treatment. PRF was performed after a positive diagnostic block in patients whose pain could not be controlled despite optimal medical treatment. The efficacy of PRF was assessed regarding pain intensity using the verbal numeric scale (VNS) and the duration of pain relief in weeks. The follow-up period was from the initial PRF procedure to the end of data collection. Parametric data were presented as mean and standard deviation (SD), and non-parametric data as median (minimum-maximum). Seventeen patients were included: 82.35% (n=14) were female, and the mean age was 58.0 ± 11.35 years. MP was present in 47.1% (n=8) and IH/IL N in 52.9% (n=9). Transverse rectus abdominis muscle flap reconstruction (TRAM) was the most common procedure (n=5, 29.41%). Diagnostic blocks were performed in 88.24% (n=15) of the patients. Initial VNS scores were 7.59 ± 2.62; 2.82 ± 2.62 at 24 hours; and 2.47 ± 1.58 at 15 days. During follow-up, 70.59% (n=12) of patients had no recurrence of initial symptoms. A second PRF was performed in 29.41% (n=5) cases based on the recurrence of symptoms, following a mean period of pain relief of 112 (8-238) weeks. No major or minor complications were identified during early or late follow-up. PRF can be a useful tool to improve the multimodal management of postsurgical abdominal wall chronic pain.

Unraveling the Tapestry of Pain: A Comprehensive Review of Ethnic Variations, Cultural Influences, and Physiological Mechanisms in Pain Management and Perception.

The medical management of pain is a nuanced challenge influenced by sociocultural, demographic, and ethical factors. This review explores the intricate interplay of these dimensions in shaping pain perception and treatment outcomes. Sociocultural elements, encompassing cultural beliefs, language, societal norms, and healing practices, significantly impact individuals' pain experiences across societies. Gender expectations further shape these experiences, influencing reporting and responses. Patient implications highlight age-related and socioeconomic disparities in pain experiences, particularly among the elderly, with challenges in managing chronic pain and socioeconomic factors affecting access to care. Healthcare provider attitudes and biases contribute to disparities in pain management across racial and ethnic groups. Ethical considerations, especially in opioid use, raise concerns about subjective judgments and potential misuse. The evolving landscape of placebo trials adds complexity, emphasizing the importance of understanding psychological and cultural factors. In conclusion, evidence-based guidelines, multidisciplinary approaches, and tailored interventions are crucial for effective pain management. By acknowledging diverse influences on pain experiences, clinicians can provide personalized care, dismantle systemic barriers, and contribute to closing knowledge gaps, impacting individual and public health, well-being, and overall quality of life.

Does Interventional Pain Management Play a Role in the Treatment of Cervical Post-Surgical Neuropathic Pain?

Post-surgical neuropathic pain is still an underdiagnosed medical condition with persistent pain occurring in 10-50% of patients submitted to surgery. We present a case of a 52-year-old patient with persistent paracervical, supraclavicular, and upper chest neuropathic pain after the excision of a massive deep right cervical tumor, concluded to be an accessory spinal nerve schwannoma. A thorough physical and ultrasound examination helped conclude injury of the superficial cervical plexus. Therefore, an ultrasound-guided hydrodissection of several neuromas was performed at the level of the superficial cervical plexus. After three procedures, pain and quality of life scores improved, with a reduction of anxiety and depression symptoms. Due to the positive response, the patient was referred for a peripheral nerve stimulator implantation, allowing self-control of pain, in a home setting.

Early Neuropathic Treatment May Prevent the Chronic Stage of Complex Regional Pain Syndrome Type II (CRPS II​).

Complex regional pain syndrome (CRPS) is a debilitating condition characterized by autonomic and inflammatory features, often caused by fractures, surgeries, or other injuries. Multimodal treatment is utilized, which often includes neuropathic medications and physical therapy. We had a case of a 24-year-old man who was diagnosed with CRPS II following an open reduction and internal fixation of a trimalleolar fracture. Significant improvement of edema, pain, and function was achieved with early initiation of gabapentin, nortriptyline, and physical therapy. In this case report, we discuss the therapeutic challenges regarding his recovery and review the literature on the utility of medications and interventional methods in treating CRPS II. We note that early treatment response may be an important prognostic indicator for the progression of CRPS II and additional studies targeting interventions for the specific type and clinical stage of CRPS are needed.

A Decade of Complex Regional Pain Syndrome Following Orthopedic Wrist Surgery: A Case Report and a Literature Review.

Every day, people of all ages in the United States break bones, with traumatic injury being the most common way, and wrist injury being in the top five most common areas in which bones break. Traumatic fractures are managed with either surgical or nonsurgical approaches. The surgical approach utilizes ortho procedures such as internal fixation and reduction, while the nonsurgical approach consists of procedures like RICE, ace bandage, and so on. However, in rare cases, patients are left with a peculiar constellation of symptoms, which cause edema, pain, skin changes, and loss of function at the trauma site. This occurrence is termed complex regional pain syndrome. Here, we present the case of a 55-year-old female patient who suffered a traumatic wrist injury. The trauma was fixed by pinning ORIF orthopedic surgery, and the patient developed manifestations of complex regional pain syndrome around 10 days postoperatively. In this case report, we describe the variation and complexity of symptoms in the patient over the course of a decade after the original injury. The case report explains the pain management therapies that reduced the patient's symptoms and highlights the ones that were ineffective. We have included some less frequently used yet effective treatments and shed light on how this disease affected the patient's overall well-being.

Intrathecal Administration of Ziconotide as a Potential Treatment for Chronic Migraines.

Migraine is one of the most prevalent and debilitating illnesses globally. There are multitudes of treatment options available for migraines. One of the emerging treatment options for migraine, refractory to conventional treatment modalities, is the intrathecal Ziconotide. Ziconotide (Prialt, Jazz Pharmaceuticals, Dublin, Ireland) enforces selective block of N-type calcium channels, which control neurotransmission at many synapses. Ziconotide is proposed to have efficacy for chronic neuropathic pain, with a favorable lack of tolerance and chemical dependency. Few studies in the literature report the successful resolution of migraine headaches with Ziconotide. The authors report the successful use of intrathecal Ziconotide therapy for chronic refractory migraines.

Treatment of Trigeminal Neuralgia With Stereotactic Radiosurgery Improved Symptoms of Morbihan Syndrome.

Trigeminal neuralgia (TN) is a neuropathic pain disorder characterized by paroxysmal pain in the maxillary and mandibular regions of the face. Morbihan syndrome is a disease that classically presents with dermatologic findings, including progressive facial edema and erythema. There are no previous reports of the onset of trigeminal neuralgia with Morbihan syndrome or previous reports describing improvement in symptoms of Morbihan syndrome with treatment of trigeminal neuralgia. We describe the case of a 62-year-old female who presented with trigeminal neuralgia and shortly thereafter developed significant facial edema and was diagnosed with Morbihan syndrome. The neuralgia was refractory to medical management and was effectively treated with stereotactic radiosurgery (SRS). This coincided with an improvement in her Morbihan syndrome that is now controlled following stereotactic radiosurgery and continued lymphatic massage.

Chronic Pain: A Complex Condition With a Multi-Tangential Approach.

Chronic pain is known as ongoing pain that lasts longer than three months with increasing healing time. It is approximated that 20% of adults of different sexes, races, and socioeconomic backgrounds fall victim to chronic pain. It is a result of several factors and can have lifelong effects. Pain is a complex matter to measure; therefore, the physician needs to understand the patient's health state to create a management plan tending to each issue adequately. There are many complications of such pain, and it can interfere terribly with an individual's quality of life. This article has reviewed the complex pathogenesis of chronic pain and the spectrum of non-pharmacologic modalities and pharmacological treatment options. It has also explored the efficacy of certain drugs and underlined the importance of nonpharmacological options such as physical exercise, cognitive therapy, and physical modalities to treat chronic pain and all the conditions that accompany this disorder.

Botulinum Toxin for the Treatment of Neuropathic Pain.

Botulinum toxin (BoNT) has been used as a treatment for excessive muscle stiffness, spasticity, and dystonia. BoNT for approximately 40 years, and has recently been used to treat various types of neuropathic pain. The mechanism by which BoNT acts on neuropathic pain involves inhibiting the release of inflammatory mediators and peripheral neurotransmitters from sensory nerves. Recent journals have demonstrated that BoNT is effective for neuropathic pain, such as postherpetic neuralgia, trigeminal neuralgia, and peripheral neuralgia. The purpose of this review is to summarize the experimental and clinical evidence of the mechanism by which BoNT acts on various types of neuropathic pain and describe why BoNT can be applied as treatment. The PubMed database was searched from 1988 to May 2017. Recent studies have demonstrated that BoNT injections are effective treatments for post-herpetic neuralgia, diabetic neuropathy, trigeminal neuralgia, and intractable neuropathic pain, such as poststroke pain and spinal cord injury.

Astrocytic expression of GFAP and serum levels of IL-1ß and TNF-α in rats treated with different pain relievers

ABSTRACT Pro-inflammatory cytokines and glial cells, especially microglial cells, have been implicated in persistent pain sensitization. Less is known about the role of astrocytes in pain regulation. This study aimed to observe the expression of the astrocytic biomarker glial fibrillary acidic protein (GFAP) and the serum levels of interleukin 1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α) after short-term administration of central pain relievers in rats not submitted to noxious stimuli. Male Wistar rats were divided into five groups, receiving for nine days- (1) amitriptyline (Amt-10 mg/kg/day, by gavage); (2) gabapentin (Gb-60 mg/kg/day, by gavage; (3) methadone (Me-4.5 mg/kg/day, intraperitoneal route [IP]); (4) morphine (Mo-10 mg/kg/day, IP); or (5) 0.9% saline solution, IP. Brain samples were collected for immunohistochemical study of GFAP expression in the mesencephalon and nucleus accumbens (NAc). The area of GFAP-positive cells was calculated using MetaMorph software and serum levels of IL-1ß and TNF-α were measured by enzyme-linked immunosorbent assay. Serum TNF-α levels were decreased in the groups treated with Mo, Me and Gb, but not in the Amt-treated group. IL-1ß decreased only in rats treated with Me. The astrocytic expression of GFAP was decreased in the brainstem with all drugs, while it was increased in the NAc with Amt, Me and Mo